An adhesive layer constituting a patch normally comprises a mixture containing a drug and, as a main component, a polymer, and with regard to means for improving the tackiness and cohesiveness of this mixture, various techniques have been carried out in which a crosslinked polymer is formed by adding an appropriate crosslinking agent during the formulation process so as to gel the adhesive layer. Such an adhesive can be obtained by a method in which a drug, etc. is added to a crosslinked polymer, but in order to add a sufficient amount of drug to the adhesive layer and solve problems in molding, a method in which an appropriate crosslinking agent is added during the formulation process to a mixture containing a drug and, as a main component, a polymer so as to gel the mixture is widely employed.
Since many of the drugs used in patches are lipophilic, various types of lipophilic acrylic polymers containing substantially no water are used as the polymer constituting the adhesive layer. In recent years in particular, this type of nonaqueous patch often contains a liquid substance as a component to improve the permeability of the drug, but this further degrades the tackiness and cohesiveness of the adhesive layer, and crosslinking of the polymer is therefore a very important object.
Crosslinking of the polymer is generally carried out by a reaction between an appropriate crosslinking agent and a crosslinking functional group of the polymer. Representative examples of the crosslinking functional group include a carboxyl group, an amino group, and a hydroxy group. Thereamong, since a hydroxy group has low reactivity compared with a carboxyl group or an amino group, there might in general be less irritation of the skin such as reddening or edema caused by residual functional groups, and it might be thought that those with a hydroxy group would be suitable for application in a patch, which needs to be affixed to the skin for a long period of time.
With regard to a crosslinking agent for a hydroxy group-containing polymer, Japanese Patent No. 2967788 proposes the use of a metal chelate, a metal alcoholate, etc., but since the metal chelate and the metal alcoholate are generally highly reactive, they might decompose or denature the drug during a crosslinking reaction, and skin irritation or more serious symptoms might be caused by residual crosslinking agent.
On the other hand, an aqueous gel is conventionally formed using, for example, a borate, a silicate, or a salt of a polyvalent metal such as calcium or magnesium, which crosslinks with a hydroxy group-containing polymer under mild reaction conditions. However, these inorganic compounds have not so far been used for the preparation of a nonaqueous gel because of problems during the preparation such as the inorganic compounds generally having poor solubility in organic solvents.
An object of the present invention is therefore to solve the problems of the prior art and provide an adhesive and a patch employing same, the adhesive having sufficient tackiness and cohesiveness as the plaster of a patch and being produced from an aqueous or nonaqueous polymer that is suitable for containing an lipophilic drug, etc.
In the present description, ‘nonaqueous polymer’ means a polymer employing, as a solvent for the polymer, an organic solvent or a mixed solvent containing an organic solvent as a main component, and ‘aqueous polymer’ means a polymer employing, as a solvent for the polymer, water or a mixed solvent containing water as a main component.